Light-Activatable Precise Synergistic Chemotherapy Through a Dual Prodrug Polymer Guided by Drug-Mediated Computed Tomography Imaging

The synergistic efficacy and clinical application of light-responsive polymeric co-delivery are severely restricted by the uncertain drug ratio and the potential adverse effects from light-responsive molecules and extra contrast agents. Here, we report the design of a dual prodrug polymer (DPP) for light-activatable precise synergistic chemotherapy guided by drug-mediated computed tomography imaging without the introduction of any extra light-responsive molecule and contrast agent. The self-assembled nanoparticle (DPP NP) was capable of triggering bioactive Pt(II) release by visible light in cancer cells/tumor, further inducing acid hydrolysis of DMC. Notably, the synergistic cancer cell killing ratio of Pt(II) and DMC in DPP NP was fixed at an optimal value even after cellular uptake, resulting in enhanced synergistic antitumor efficacy in vitro and in vivo. Due to the high content of heavy metal Pt in the polymer chain, the spatial/temporal dynamic bio-distribution as well as metabolism of DPP NP in tumor can be monitored via Pt drug-mediated computed tomography (DMCT) imaging to guide the illumination parameters for optimized light-activatable synergistic chemotherapy. Guided by Pt DMCT imaging, DPP NP showed an excellent light-activatable antitumor efficacy and low toxicity with 75% fully cured tumors. The light-activatable dual drug polymer system could be potential for precise theranostic nanomedicine.